T-HELPER-1 EFFECTOR-CELLS SPECIFIC FOR HELICOBACTER-PYLORI IN THE GASTRIC ANTRUM OF PATIENTS WITH PEPTIC-ULCER DISEASE

Chronic antral gastritis following Helicobacter pylori (Hp) infection is characterized by a cellular inflammatory infiltrate whose cytokines may represent a host-dependent factor influencing the outcome of the infection. The pattern of cytokines produced by the immunologically ac tive cells in the gastric antrum was analyzed at the mRNA level in ant ral biopsies from five Hp-infected patients with duodenal ulcer and th ree Hp-negative dyspeptic controls. T cell clones were generated from parallel antral biopsies of the same Hp-infected patients and assessed for reactivity to Hp Ags, cytokine profile, and effector functions. A ntral biopsies from all Hp-infected patients showed lFN-gamma, TNF-alp ha, and IL-12, but not IL-4, mRNA expression, whereas no cytokine mRNA signal was found in the mucosa of controls. A total of 24 out of the 163 CD4(+) T cell clones (15%) derived from Hp-infected patients proli ferated in response to a Hp lysate; 11 clones (46%) also reacted with Gag-A, 2 with Vac-A, and 1 with urease. Upon Ag stimulation, 20 out of the 24 Hp-reactive clones (83%) produced IFN-gamma, but not IL-4 or I L-5 (Th1-like), whereas 4 produced IFN-gamma, IL-4, and IL-5 (Th0-like ). All Hp-specific clones secreted high levels of TNF-alpha, At low T: B cell ratio, Hp-specific clones expressed Ag-dependent helper,functio n for B cell proliferation and Ig production, whereas at higher T:B ce ll ratios, 15 Th1 and 2 Th0 clones lysed Ag-pulsed autologous EBV-tran sformed B cells. Results provide evidence for Hp-specific Th1 effecter s in the gastric antrum of Hp-infected patients, where they may play a role in the genesis of either peptic ulcer or Hp-associated gastric B cell lymphoma.